PROJECT SUMMARY/ABSTRACT ? Resource Core 2: Cellular Systems Core Investigators in the Joint Biology Consortium (JBC) share a set of technical challenges that impede utilization of state-of-the-art human and murine cell analysis for arthritis research. To overcome these hurdles, the Cellular Systems Core (CSC) will leverage economies of scale to develop an integrated set of research tools to serve JBC members across 17 centers. The CSC will provide four distinct but interrelated services. First, the Brigham and Women's Human Immunology Center will become the central collection and processing site for human samples, enabling not only logistically simplified collection but also specialized handling of synovial tissues as well as cells intended for high-resolution single-cell analysis. Second, the CSC will support optimized cytometry by time of flight (CyTOF), including arthritis-related antibody panels, rare earth metal conjugation, barcoding, and data analysis. Third, the CSC will simplify access to single-cell and low-input RNA-seq through the Broad Institute, including first access to Drop-seq and related methods and analysis. Finally, recognizing the ongoing importance of murine translation for pre-clinical research, the CSC will provide centralized development and CRISPR/Cas9 genetic manipulation of experimental model cells using innovative HoxB8 technology, ideal for in vitro and in vivo investigation of the biology of cells lineages including neutrophils, monocyte and osteoclasts. Progressive optimization of CSC services will result not only from JBC member studies but, importantly, through technical coordination with the Accelerating Medicines Partnership (AMP) in arthritis research, ensuring that JBC members have access to the latest methodologic advances. Service delivery will be led by a senior scientific team consisting of Harvard CyTOF director Dr. James Lederer, supported by associate directors Dr. Chad Nusbaum of the Broad Technology Labs and Dr. Peter Nigrovic at BWH/Children's. This team will ensure that the logistical investment represented by the Cellular Systems Core will accelerate innovative translational arthritis research within the JBC.